Viral Pathogenesis

Excerpt

Pathogenesis is the process by which virus infection leads to disease. Pathogenic mechanisms include implantation of the virus at a body site (the portal of entry), replication at that site, and then spread to and multiplication within sites (target organs) where disease or shedding of virus into the environment occurs. Most viral infections are subclinical, suggesting that body defenses against viruses arrest most infections before disease symptoms become manifest. Knowledge of subclinical infections comes from serologic studies showing that sizeable portions of the population have specific antibodies to viruses even though the individuals have no history of disease. These inapparent infections have great epidemiologic importance: they constitute major sources for dissemination of virus through the population, and they confer immunity (see Ch. 48).

Many factors affect pathogenic mechanisms. An early determinant is the extent to which body tissues and organs are accessible to the virus. Accessibility is influenced by physical barriers (such as mucus and tissue barriers), by the distance to be traversed within the body, and by natural defense mechanisms. If the virus reaches an organ, infection occurs only if cells capable of supporting virus replication are present. Cellular susceptibility requires a cell surface attachment site (receptor) for the virions and also an intracellular environment that permits virus replication and release. Even if virus initiates infection in a susceptible organ, replication of sufficient virus to cause disease may be prevented by host defenses (see Chs. 49 and 50).

Other factors that determine whether infection and disease occur are the many virulence characteristics of the infecting virus. To cause disease, the infecting virus must be able to overcome the inhibitory effects of physical barriers, distance, host defenses, and differing cellular susceptibilities to infection. The inhibitory effects are genetically controlled and therefore may vary among individuals and races. Virulence characteristics enable the virus to initiate infection, spread in the body, and replicate to large enough numbers to impair the target organ. These factors include the ability to replicate under certain circumstances during inflammation, during the febrile response, in migratory cells, and in the presence of natural body inhibitors and interferon. Extremely virulent strains often occur within virus populations. Occasionally, these strains become dominant as a result of unusual selective pressures (see Ch. 48). The viral proteins and genes responsible for specific virulence functions are only just beginning to be identified.

Fortunately for the survival of humans and animals (and hence for the infecting virus), most natural selective pressures favor the dominance of less virulent strains. Because these strains do not cause severe disease or death, their replication and transmission are not impaired by an incapacitated host. Mild or inapparent infections can result from absence of one or more virulence factors. For example, a virus that has all the virulence characteristics except the ability to multiply at elevated temperatures is arrested at the febrile stage of infection and causes a milder disease than its totally virulent counterpart. Live virus vaccines are composed of viruses deficient in one or more virulence factors; they cause only inapparent infections and yet are able to replicate sufficiently to induce immunity.

The occurrence of spontaneous or induced mutations in viral genetic material may alter the pathogenesis of the induced disease, e.g. HIV. These mutations can be of particular importance with the development of drug resistant strains of virus.

Disease does not always follow successful virus replication in the target organ. Disease occurs only if the virus replicates sufficiently to damage essential cells directly, to cause the release of toxic substances from infected tissues, to damage cellular genes or to damage organ function indirectly as a result of the host immune response to the presence of virus antigens.

As a group, viruses use all conceivable portals of entry, mechanisms of spread, target organs, and sites of excretion. This abundance of possibilities is not surprising considering the astronomic numbers of viruses and their variants (see Ch. 43).